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- W2536707093 abstract "The locus coeruleus (LC) as the only source for norepinephrine (NE) in the human brain shows early degeneration in Alzheimer’s disease (AD). The LC-NE system is involved in attentional processes and different behavioral and functional markers (e.g. evoked EEG potentials, BOLD responses, pupillary dilatation) have been identified as potential markers for LC-NE-functionality. Here, we assessed whether these markers are characteristically altered in AD, thus providing potential surrogate markers for interventional trials targeting the LC-NE-system. We aim at including patients (planned: n=30) with cerebrospinal fluid-biomarker evidence for AD and age-matched healthy controls (planned: n=30). We obtain reaction times and accuracy, event-related electroencephalography (EEG) potentials (P300b), task-related pupil dilation and event-related blood oxygen level dependent (BOLD) responses in a stimulus detection task (Oddball-paradigm). Additionally, structural magnetic resonance imaging (MRI) with neuromelanine-sensitive sequences is applied to determine a volumetric measure for the LC. Here, we present preliminary results for 15 subjects with AD and 25 control subjects. On behavioral level AD patients had longer reaction times compared to the control group while accuracies were similar. In controls, the Oddball-paradigm induced a bilateral frontoparietal BOLD response with a strong response in the dorsal pons (LC region). In AD patients the cortical response was less extended and the dorsal pontine response was decreased. The amplitudes of the P300b and the pupil response were reduced in AD patients. Unexpectedly, the P300b in AD subjects had a shorter latency compared to the controls. In pupillometric data, the latency was slightly longer in AD patients. In structural MRI larger LC volumes were observed for the left LC in the control group compared to AD subjects. Our preliminary results show alterations in behavioral and functional parameters in a signal detection task that are consistent with hypothesis (exception: shorter latency of P300b in AD patients). Our results demand confirmation in a larger sample and a demonstration that the parameters are sensitive to pharmacological manipulations of the NE systems. We suggest that these parameters might be suitable surrogate markers for pharmacological interventions targeting the LC-NE-system in AD." @default.
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- W2536707093 date "2016-07-01" @default.
- W2536707093 modified "2023-09-28" @default.
- W2536707093 title "P1-223: Functional Markers for Cerebral Norepinephrine Deficiency in Alzheimer’s Disease" @default.
- W2536707093 doi "https://doi.org/10.1016/j.jalz.2016.06.972" @default.
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